1. Field of Invention
This invention relates to products and methods useful in the prevention and/or treatment of peritonitis conditions such as that which occurs as a consequence of the administration of peritoneal dialysis treatments.
2. Prior Art
The historical transition of peritoneal dialysis from a first clinical attempt in 1923 to a viable life-support system for current patients suffering from renal failure or similar life threatening disorders has been marked with numerous problems which have challenged its acceptance by the medical profession. Chief among these obstacles has been an unacceptably high incidence of peritonitis induced by entry of pathogenic bacteria through access sites used for infusion of dialysate fluids. This "dialysis induced" peritonitis is to be distinguished from "surgical" peritonitis which often accompanies rupture of viscera such as appendix, gall bladder, bowel, etc. Surgical peritonitis presents a uniquely distinguishable environment because of the considerable amount of debris (pus, fibrin and pieces of necrotic tissue) which is contained within the peritoneal cavity.
Dialysis induced peritonitis, however, refers to inflammation of the peritoneum and viscera contained therein by bacteria or fungi, in the absence of concurrent tissue damage, such as from rupture or perforation. Vaamonde et al, for example, have demonstrated that as many as 25% positive cultures of organisms have been present in sample fluids of 142 dialyses. Of these patients with positive cultures, 6.3% contracted clinical peritonitis, an overall incidence rate of 1.6%. Vaamonde, Michael, Metzger, Carroll, "Complications of Acute Peritoneal Dialysis," J Chron Dis 28: 637, 1975. The actual probability of occurrence of dialysis induced peritonitis (hereinafter referred to as "DIP") varies with different methods of peritoneal dialysis.
Peritoneal dialysis was originally accomplished by the manual exchange technique with the use of hanging bottles (1 liter volume) whose contents drained into the peritoneal cavity by means of a catheter. Since a considerable volume of dialysate was normally required, several changes of bottles occurred during each treatment. Because of the high incidence of peritonitis (3%-10% of all dialysis performed) new methods were developed to avoid the use of 1 liter bottles. Fluid delivery systems were automated and coupled to a large reservoir (40 liters) or dialysate proportioning systems which reduced the number of connect-disconnect steps, with an accompanying reduction in exposure to hostile bacteria. With increased attention to strict sterile techniques, these procedures reduced infection rates down to about 0.2% of the total number of dialyses performed.
These two procedures remained as the primary peritoneal dialysis techniques for many years. Government financial assistance became available for patients suffering from End Stage Renal Disease (ESRD) in 1973. With this added financial support, many more patients turned to dialysis centers for life support treatment. As many as 40,000 patients in the U.S.A. are currently relying on dialysis as a life support system, and the number continues to grow. Treatment options available to those patients treated by peritoneal dialysis consist of (1) use of expensive automated equipment, either in a dialysis center or at home, or (2) use of 2 liter bottles or plastic bags of sterile dialysate as a manual exchange method. Neither alternative is pleasant, in view of the life-long inconvenience and expense of the former automated method and the high risk of peritonitis associated with the latter manual exchange method.
In 1977, a variation of the manual exchange method was introduced under the description "Continuous Ambulatory Peritoneal Dialysis" (CAPD). This method provides continuous presence of dialysate within the peritoneal cavity, except during periods of drainage and instillation of fresh solution which is to be effected 4-5 times daily. Using this method the patient experiences new freedom and demonstrates better health and improved appetite. This results, in part, from the fact that the patient is able to perform the drainage and refill within the comfort of his own home without the necessity of installing expensive immobilizing, high technology equipment.
Despite the improvement of CAPD in methodology, the risks of peritonitis are still a major obstacle to acceptance of nonautomated dialysis procedures. It therefore appears that CAPD and similar manual exchange methods can only be successful if techniques for prevention and treatment of DIP are realized. This conclusion is verified by the following experience reports:
1. One group of patients treated under CAPD contracted DIP on the average of once every 10 weeks. Popovich, Moncrief, Nolph, Ghods, Twardowski, Pyle, "Continuous Ambulatory Peritoneal Dialysis," Ann Intern Med., 88,4: 449-456, Apr. 1978. This was later improved to a 1 in 14 weeks average. PA1 2. In a second group practising CAPD, of 41 original patients, five withdrew permanently. Seven others discontinued CAPD on a temporary basis due to DIP. Robson, Oreopoulos, "Continuous Ambulatory Peritoneal Dialysis: A Revolution in the Treatment of Chronic Renal Failure," Dialy & Transp 7,10: 999-1003, Oct 1978. PA1 3. The present inventors, after introducing a subcutaneous catheter method, dialyzed 45 patients by manual exchange for a total of 490 patient weeks (approx. 1470 dialyses). Sixteen episodes of DIP occurred, a rate of 1.1% of all dialyses performed. PA1 1. Preparing a first physiological solution which is free of protein material and of reducing substances which are capable of converting I.sub.2 or HIO to I.sup.- ; PA1 2. Preparing a second physiological solution having a combined I.sub.2, HIO concentration in the range of 0.1 to 15 ppm; PA1 3. Flushing a patient's peritoneal cavity with said first solution to remove materials comprising said reducing substances and protein material contained within said cavity; and PA1 4. Contacting said cavity with said second solution for a period of at least 30 seconds.
Although improved techniques have reduced DIP from the original 3-10% rate incurred during manual exchange peritoneal dialysis, the 0.2 to 0.3% rate of automated dialysis still remains the safest of peritoneal dialysis methods. Therefore, assuming that time on such machines is available, patients must determine whether they can accept the inconvenience and immobilization attendant upon the use of a large and noisy dialysis machine, or assume both the freedom and the risk of DIP accompanying manual exchange techniques.
Once contracted, DIP generally requires extended treatment with antibiotics specifically selected for the infecting bacteria. Such treatments usually require several weeks and are complicated by the fact that DIP may be caused by numerous organisms, including staphylococcus aureus, Klebsiella, staphylococcus epidermidis, dipheroids, E. coli, streptococcus fecalis, pseudomonas, fungi and even mycobacteria (tuberculosis-like organisms). Although treatment by use of antibiotics is effective, prevention with antibiotics remains impractical because of the many types of possible infections organism. With respect to DIP patients, both prevention and treatment are particularly significant because peritonitis threatens the very existence of the patient's critical life-support system.